Stage IV Distal Bile Duct Cancer AJCC v8

This phase II/III trial studies how well the addition of ivonescimab to standard chemotherapy (gemcitabine and cisplatin) works when compared to usual chemotherapy and immunotherapy (durvalumab or pembrolizumab) in treating patients with biliary tract cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab is a bispecific antibody that is directed against both the programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF) protein. By targeting PD-1, ivonescimab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. By targeting VEGF, ivonescimab may help stop the formation of blood vessels that bring oxygen and nutrients to tumor. Adding ivonescimab to standard chemotherapy may work better than usual chemotherapy and immunotherapy in lowering the chance of advanced biliary tract cancer growing or spreading.

This phase I trial studies the side effects of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) nab-paclitaxel in combination with gemcitabine and cisplatin in treating patients with biliary tract cancer that has spread to the peritoneum (peritoneal metastases). PIPAC involves the administration of intraperitoneal chemotherapy (anticancer drugs given directly to the lining of the abdomen). PIPAC uses a nebulizer (a device that turns liquids into a fine mist) which is connected to a high-pressure injector and inserted into the abdomen (part of the body that contains the digestive organs) during a laparoscopic procedure (a surgery using small incisions to introduce air and insert a camera and other instruments into the abdominal cavity for diagnosis and/or to perform routine surgical procedures). Pressurization of the liquid chemotherapy through the study device results in aerosolization (a fine mist or spray) of the chemotherapy intra-abdominally (into the abdomen), which results in the drug reaching more of the tissue as well as reaching deeper into the tissue, which reduces the amount of chemotherapy that needs to be used and potentially reduces side effect. Chemotherapy drugs, such as nab-paclitaxel, gemcitabine, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nab-paclitaxel via PIPAC in combination with standard of care gemcitabine and cisplatin may reduce side effects and make this chemotherapy regimen more tolerable in patients with biliary tract cancer that has spread to the spread to the peritoneum.